Two different forms of death are commonly observed when Mycobacterium tuberculosis (Mtb)-infected macrophages die: (i) necrosis, a death modality defined by cell lysis and (ii) apoptosis, a form of death that maintains an intact plasma membrane. Necrosis is a mechanism used by bacteria to exit the macrophage, evade host defenses, and spread. In contrast, apoptosis of infected macrophages is associated with diminished pathogen viability. Apoptosis occurs when tumor necrosis factor activates the extrinsic death domain pathway, leading to caspase-8 activation. In addition, mitochondrial outer membrane permeabilization leading to activation of the intrinsic apoptotic pathway is required. Both pathways lead to caspase-3 activation, which results in apoptosis. We have recently demonstrated that during mycobacterial infection, cell death is regulated by the eicosanoids, prostaglandin E2 (proapoptotic) and lipoxin (LX)A4 (pronecrotic). Although PGE2 protects against necrosis, virulent Mtb induces LXA4 and inhibits PGE2 production. Under such conditions, mitochondrial inner membrane damage leads to macrophage necrosis. Thus, virulent Mtb subverts eicosanoid regulation of cell death to foil innate defense mechanisms of the macrophage.

No abstract

Radiation doses to both the fingertip and finger base of staff preparing radiopharmaceuticals in a radionuclide dispensary have been monitored for more than 5 years. The records show a fall in dose thought to be due, largely, to the introduction of all-glass (lead) syringe shields. In 1998, the annual radiation dose (mean +/- standard deviation) to the fingertip had fallen to 83+/-11 mSv, which corresponded to 0.18 mSv per 10 GBq 99Tc(m) handled. There was less reduction in dose to the finger base, which, in 1998, was 70% of that to the fingertip. To study the effect of a syringe shield on the distribution of dose across the hands, model hands were constructed and a gamma extremity monitoring system (GEMS) was used to measure dose. When a radiopharmaceutical is dispensed, contributions to the dose from activity in the vial and syringe change during the procedure. As a result, relative doses to different fingers and the ratios of doses to the tip and base of each finger will fluctuate throughout dispensing. In the absence of a syringe shield, the front tip of the index finger received the greatest radiation dose. When a syringe shield was used, doses were lower and the dose distribution was completely different. These findings have important implications in terms of compliance with the new UK Ionizing Radiations Regulations, where the dose limit is applied to 'the dose averaged over any area of 1 cm2 regardless of the area exposed'.

No abstract